There have been many recent advances in the area of photomedicine for the treatment of superficial lesions, including treatment of precancerous and cancerous lesions using photocoagulation (PC), thermotherapy (TT), and photodynamic therapy (PDT). These three types of treatment utilize very different mechanisms, but all involve administering light to the target tissue to affect therapy. The term superficial lesion is understood here to mean that the lesion is on or near the surface of target tissue and thereby accessible to light that is administered to the target tissue surface. For example, in ophthalmology, all three treatment approaches are being used in the treatment of age-related macular degeneration (ARMD), a leading cause of irreversible visual loss. Likewise, in dermatology, PDT is presently being used to treat melanoma, non-melanoma, actinic keratoses, as well as both basal and squamous cell carcinomas. PC is presently being used to remove vascularities. Other areas of treatment that can benefit from the above listed approaches include, but are not limited to, gynecology, gastroenterology, and thoracic surgery. Although the details of the approaches vary due to the anatomical differences presented, the fundamental underpinnings are the same. That is, one must provide treatment light to the targeted lesion. To date, this has been done primarily with broad-brush application of light to the lesion and its surrounding tissue. While this has the advantage of being straightforward, it also limits the ultimate clinical efficacy by increasing the side effect profile. This is because these therapies are not sufficiently site selective in their efforts. The irradiation of adjacent tissue causes more damage than is necessary. Therefore, a more selective approach to delivering therapeutic light to lesions is needed, which minimizes the irradiation of adjacent, non-targeted tissue.
The light sources used for these different therapies may be continuous wave (cw) where the light is produced and delivered in a continuous, uninterrupted manner, or quasi-cw which is where the light is modulated at a pulse repetition frequency (PRF) too high to be distinguished from cw light in terms of its effect on the target tissue (for the purposes of this disclosure at or above 2 KHz). Examples of the three major photomedical therapies mentioned above are now described in more detail below.
1. Photocoagulation
Retinal photocoagulation may be performed at a variety of wavelengths. The light need only be primarily absorbed by the targeted chromophore, and not its surroundings. The targeted chromophore is often the melanin resident in the retinal pigment epithelium (RPE). Retinal photocoagulation is typically performed using green light, because of melanin's high absorption of light in this wavelength range. However, blood strongly absorbs light below 600 nm. To accommodate this, longer wavelength light is often used when blood is present in the aqueous humor. FIG. 1 shows the optical absorption properties of the predominant autogenous ocular chromophores; namely melanin in the RPE, oxy-hemoglobin (HbO2), and deoxy-hemoglobin (Hb), as compared to epidermis. The successful clinical use of red light to affect photocoagulation by targeting melanin has been well established using both 647 & 810 nm light from Krypton ion & semiconductor lasers, respectively. The choices of these wavelengths has been historically based upon the availability of light sources at these wavelengths, and not necessarily by the spectroscopic properties of the target tissue. Because of the monotonic character of melanin's optical absorption, and the lack of sufficient absorption in blood or water, red light photocoagulation can be effectively performed with light within the range of 600-900 nm.
2. Thermotherapy
In the context of ophthalmology, transpupillary thermotherapy (TT) is the slow heating of the subfoveal choroidal neovascular complex to occlude CNV (Choridal Neovascularization). An 810 nm laser diode system has been used as the light source, where the light is delivered in a large single round spot that covers the entire treatment complex. With properly selected small choroidal melanomas, tumor control has proven to be excellent. The heat induces cellular damage at the site of treatment with few remote side effects. However there are often complications adjacent to the site of treatment, including retinal vascular obstruction, and retinal traction.
3. Photodynamic Therapy
Photodynamic Therapy (PDT) is currently practiced by injecting a photoactivation drug that specifically binds to diseased tissues, and is sensitive to certain wavelengths of light for subsequent photoactivation to produce highly reactive byproducts, such as singlet oxygen. After injecting a photoactivation drug, a physician then typically irradiates a portion of the tissue that is considerably larger than necessary for a period sufficient to realize the therapeutic photochemistry. This broad-brush approach generally tends to minimize the losses due to optical scattering. However, with the relatively long wavelengths used for PDT, optical scattering is less of a concern than it is for other therapies. Below is a table of photoactivation drugs and their excitation wavelengths that have been used in PDT:
Photoactivation Drugλ [nm]DHE630HP630HpD630PF630PpIX630Chle6662SnET2664ATXSI0670AlS4Pc673CASPc675BPDMA690LuTex732Bacteriochlorina760SINc779
PDT has been used to treat a variety of conditions, such as Barrett's esophagus, esophageal adenocarcinoma, uveal melanoma, retinoblastoma, choroidal neovascularization, melanoma, non-melanoma, actinic keratoses, and both basal and squamous cell carcinomas. However, PDT has yet to be optimized. Today, physicians typically treat their PDT patients by adhering to a rigid protocol under which the laser spot size, treatment time, and laser power are all fixed. Although there have been feedback mechanisms proposed for PDT, none are known to have been clinically implemented. Such feedback mechanisms would only improve the overall effectiveness of any approach.
Because photoactivation drugs used are not perfectly selective, PDT can cause damage to adjacent healthy tissue. A measure of this selectivity is the “retention ratio,” a value defined as the ratio between the photoactivation drug concentration in diseased tissue to that of the adjacent normal tissue. Typical retention ratio values ranging from 2 to 5 have been reported. Therefore, some amount of healthy tissue immediately surrounding the targeted lesion tissue must be sacrificed to assure that the entire population of diseased cells has been eradicated. However, as illustrated in FIG. 2, the irradiation geometry of the applied light 1 is typically circular, while the lesions 2 generally are not circular. Thus, the drug's imperfect retention ratio and the light source's large, circular spot together create relatively large amounts of unwanted cellular damage adjacent to the target lesion.
One attempt to reduce adjacent tissue damage has been to scan the light beam across the lesion in a pattern that generally covers the surface area of the lesion. For example, a discontinuous raster scan pattern has be used to sweep the beam across the lesion in successive rows. However, such scans have been performed in simple geometries (such as squares and hexagons) which again bear little relation to the arbitrary shape of the lesion. Such scans also include excessive numbers of discontinuities between multiple scans adding inefficiency and possible sources of error to the treatment.